Mesenchymal Stem Cell Secretome in Tendon Regeneration: Therapeutic Potential, Mechanisms of Action, and Future Perspectives

Tendon injuries are common and debilitating musculoskeletal conditions that impose pain and debilitation to patients, significant challenges to medical professionals, and financial burdens to the healthcare system. Due to limited natural healing capacity, tendons typically undergo scar-mediated repair that compromises biomechanical integrity and increases the risk of reinjury. Despite a variety of therapeutic strategies, functional tendon healing remains a major clinical challenge. Mesenchymal stem cells (MSCs) represent an attractive strategy to improve tendon healing, largely due to their immunomodulatory and regenerative properties. Increasing evidence suggests that the therapeutic potential of MSCs is primarily attributed to their paracrine activity via the release of the secretome, a set of bioactive molecules that are known to mimic the immunomodulatory and regenerative properties of their parental cells. More recently, acellular approaches using MSC secretome derivatives, such as conditioned media and extracellular vesicles, have been largely explored for tendon healing. This review of the literature explores the therapeutic potential of MSC secretome derivatives for tendon healing, highlighting their advantages over cell-based therapies, proposed mechanisms of action, manufacturing and scalability considerations, and current state of research.